The goal of my research proposal is to understand the molecular mechanisms underlying the transmembrane translocation of solutes by the Major Facilitator Superfamily (MFS) of transporters. MFS transporters are the largest family of transporters classified to date, and includes at least 28 subfamilies and several thousand proteins. These transporters can translocate an extraordinary variety of solutes, yet are still proposed to share a common evolutionary background and structural architecture. The primary technique that will be employed for my research will be that of x-ray crystallography. I intend to improve my chances of success in this project by using many prokaryotic homologs for crystallization trials. Ten prokaryotic homologs have already been expressed to high levels, and preliminary crystals have been grown for several of these homologs. Crystallographic analysis of any one MFS transporter will reveal insight into the function of this entire class of important proteins.